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PubMed1995

Multicentre trial of antepartum low-dose anti-D immunoglobulin.

Routine antenatal Rh immunoprophylaxis would substantially increase the use of anti-D Ig in the U.K. As availability of anti-D Ig is one factor influencing a decision to introduce routine antenatal prophylaxis, a trial was undertaken to test the efficacy of a lower dose of anti-D Ig than that used in earlier studies. RhD-negative primigravidae were randomized as controls or recipients of two doses of 250iu of anti-D Ig given at 28 and 34 weeks gestation. Blood samples were tested at delivery and at 6 months postpartum for the presence of immune anti-D, and again later if results were equivocal. Nine (1.5%) out of 595 control patients had immune anti-D at follow-up at 6 months and later; 4 (0.78%) of 513 treated women were immunized. It was concluded that, while two doses of 250iu of anti-D Ig may reduce alloimmunization, they are not as effective as two doses of 500iu in a previous trial.

Dose-Response Relationship, Drug↗
PubMed1986

Rhesus immunization after Rh-incompatible kidney transplantation.

Rh-immunization of a male recipient was observed following the transplantation of two kidneys from Rh-pos donors. Immunosuppression consisted of azathioprine, prednisone and antilymphocyte globulin (1st transplantation) and cyclosporin A and prednisone (2nd transplantation). The immunization was probably caused by the residual blood in the cadaver kidneys. The use of cyclosporin A might increase the risk of Rh-immunization.

Adult↗
PubMed1995

HLA phenotypes and severe Rh(D) immunization.

Blood samples from 24 Rh(D) immunized women were analyzed for antibody titers and quantification of anti-D. The HLA-DR and -DQ polymorphisms were identified as RFLP. In 11 women with titers 16-256 the HLA-DQB1 allele *0201 was found in 18%, i e as in a reference population. In 13 women with titers > or = 512 the HLA-DQB1 allele *0201 was found in 85% indicating a correlation between severe Rh(D) immunization with high titers/quantification values and the DQB1 allele *0201. In this group the fetus was severely affected by the immunization and treatment during pregnancy was frequently needed. HLA phenotyping of women known to have anti-D antibodies early in pregnancy seems to be an effective way to assess the probability of severe hemolytic disease of the newborn.

Alleles↗
PubMed1986

Fetomaternal transplacental hemorrhage during pregnancy and after delivery.

One third of very weakly Rh-immunized women show no increase in their level of Rh immunization during pregnancy and after delivery. Administration of 300 micrograms of Rh immune globulin at 6-week intervals does not alter the incidence of lack of progression of Rh immunization in such women. Thirty-three Rh-positive women who ultimately delivered ABO-compatible babies, had Kleihauer fetal transplacental hemorrhage (TPH) screening tests carried out at 2-week intervals during pregnancy and shortly after delivery. One third of the 33 women had no detectable TPH or a TPH of 0.01 ml of fetal red cells. We conclude that one third of weakly Rh-immunized women failed to show any progression of their Rh immune response during pregnancy or after delivery because they were exposed to too few fetal red cells (0.01 ml or less) to produce such a response.

ABO Blood-Group System↗
PubMed1986

Fetomaternal AB0 incompatibility and erythroblastosis fetalis.

Ninety-one of 330 fetuses undergoing intrauterine fetal transfusion (IUT) had sufficient residual fetal red cells in their cord blood samples that their AB0 blood groups could be determined. Ten of the 91 (11%) were AB0 incompatible with their mothers. The degree of Rh disease was severe in all 10. Three were hydropic in utero; 5 had the syndrome of hepatocellular damage; in 6, IUT were required between 22 and 26 weeks gestation. The expected incidence of AB0 incompatible pregnancies in which the fetuses required IUT if AB0 incompatibility had no effect on severity of Rh disease, is 9.7% versus the 11% observed. AB0 incompatibility has no effect on ameliorating severity of erythroblastosis after Rh immunization has developed. AB0 incompatibility between mother and father should not be taken into account when making decisions regarding the management of an Rh immunized pregnancy.

ABO Blood-Group System↗
PubMed1987

Transfusion significance of LWa allo-antibodies.

An example of anti-LWa, arising as a complication during a RhD immunization programme, has been studied for evidence of its likely in vivo haemolytic properties. In vitro testing of the anti-LWa showed it to be largely IgG1 acting by the antiglobulin technique. Results of antibody-dependent cellular cytotoxicity and macrophage phagocytic assays were both negative. However, 99mTc-labelled Lw(a+) donor cells showed a slight reduction in t1/2 (18 h) compared with the normal survival of autologous cells. Despite this observation, and bearing in mind the difficulties of interpreting apparently accelerated destruction of small serologically incompatible red cells, it was concluded that the presence of this example of anti-LWa should not be a bar to urgent transfusion.

Aged↗
PubMed1988

Management of serious alloimmunization in pregnancy.

In the past 40 years, tremendous advances in the treatment of hemolytic disease have been made. The perinatal mortality has been reduced considerably. Rh immunoprophylaxis has decreased the incidence of Rh immunization to around 6 per 100,000 live births. Nevertheless, treatment of severe hemolytic disease is still essential. Increased reliability of diagnostic procedures have made early detection and optimal treatment of hemolytic disease possible. Treatment by plasmapheresis is still controversial. Although believed to be beneficial by some authors, conclusive evidence of its efficacy has not been obtained. With preterm induction of birth at 32 weeks of gestation, the chances for survival are 95%. Improvement of techniques and the use of modern real-time ultrasound equipment have made intrauterine intraperitoneal transfusion, in experienced hands, a relatively safe and successful procedure. Intravascular transfusion appears beneficial in early pregnancy. Combination of both techniques will probably be the answer for the future. The development of neonatal intensive care facilities has made a major contribution to the survival of children with haemolytic disease. The relative low incidence of haemolytic disease has made it imperative that treatment should take place in centers where experience and special skill are available.

Female↗
PubMed1991

Intravenous drug abuse causes Rh immunization.

Intravenous drug abuse causes many health problems. From March 1989 to January 1990 of 27 Rh-negative women (28 pregnancies) referred to our centre, 4 women (5 pregnancies) were Rh immunized due to the sharing of needles and blood with their Rh-positive partners. Severe hydrops was present in 4 of their 5 fetuses when they were first seen at 17-35 weeks of gestation. Only the fetus first seen at 35 weeks survived. That infant was moribund at birth and now has evidence of leukomalacia and porencephaly. The fifth fetus, not hydropic, required two intravascular fetal transfusions in order to survive. A fifth woman, immunized in a similar manner, had a spontaneous abortion. These fetuses represent some of the earliest and severest examples of hydrops fetalis ever seen at our centre. The severity of their fetal hemolytic disease is probably due to the fact that their mothers' exposure to Rh(D) antigen by blood sharing was continuous and ongoing. Because of their aberrant behaviour, these women have suffered irreversible reproductive damage.

Abortion, Spontaneous↗
PubMed1991

Successful treatment of severe Rh iso-immunization with immunosuppression and plasmapheresis.

Nine patients with severe Rh iso-immunization were treated by plasma exchange combined with immunosuppression. Apart from 3 abortions, previous pregnancy losses consisted of 7 intra-uterine and 5 neonatal deaths. Only 2 patients had had no previous pregnancy loss. Differences in the optical density of the amniotic fluid of 8 patients fell into the upper Liley zone. There was one intra-uterine death due to abruptio placentae but no neonatal deaths. When the outcome of the pregnancy immediately preceding the treatment pregnancy was compared to the treatment pregnancy, the fetal loss was reduced from 6 to 1. No adverse fetal effects were encountered.

Adult↗
PubMed1991

High-dose intravenous IgG for the treatment of severe rhesus alloimmunization.

The value of intravenous immunoglobulin (IVIG) in the treatment of 24 severely Rh-sensitized pregnant women was studied. IVIG was infused at a daily dose of 0.4 g/kg maternal body weight for 4-5 consecutive days, and was administered again 15-21 days later until delivery, depending on the evolution of the hemolytic disease. Our population was divided into 3 groups according to the time of onset of therapy: group 1 (n = 8), before 20 weeks' gestation; group 2 (n = 7), 20-28 weeks, and group 3 (n = 9), after 28 weeks. Initial mean anti-D level was significantly higher in group 1 (25.9 +/- 12.9 IU/ml) than in the other 2 groups, whose mean values were, however, higher than 10 IU/ml. Amniotic-fluid total bilirubin levels before the onset of therapy were pathologic, and in 55% of the cases they coincided with zone 3 of Liley's chart. Hydrops fetalis at the onset of treatment accounted for the only 3 fetal deaths in groups 1 and 2. None of the fetuses developed hydrops during treatment. Six of the 9 neonates in group 3 were depressed at birth (1-min Apgar below 7). However, at 5 min only 1 newborn showed an Apgar below 7. Mean birth weight was over 2,500 g in all the cases. Neonatal hematological condition in group 2 (50% of the babies required only phototherapy) was better than in the other 2 groups (transfusional therapy). There was a significant fall in maternal anti-D titers and intrauterine hemolysis after IVIG treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1994

Human monoclonal antibodies against the rhesus D antigen from women with severe Rh immunization submitted to high-dose intravenous immunoglobulin treatment.

The pre- and postpartum maternal serum anti-D concentrations of 28 women with severe Rh(D) immunization who received high-dose intravenous immunoglobulin treatment has been determined. In all cases, including 1 in which the newborn was D negative, a sharp increment in the anti-D titer was observed after delivery. The specific immunoglobulin concentration rose to levels ranging from 4.7 to 204.0 micrograms/ml and, in 20% of the patients, increments of fifty times or greater were observed. Human monoclonal antibodies (hmAb) have been produced from Epstein-Barr virus-transformed lymphoblastoid B cell lines derived from 1 of these naturally hyperimmunized patients whose serum contained an anti-D-category DVI antibody. Four anti-D-secreting cell lines (97.E3.39.214, 44.E4.R1.257, E7.R1.126.83.115 and E11V.117.63; hereafter referred to as 214, 257, 115 and 63) have been established and maintained in continuous culture for periods ranging from several months to 3 years, without loss of antibody production capacity. Antibodies 115 and 214 recognize all Du samples tested at the same level as the polyclonal positive control. Antibodies 63 and 257 show a significantly lower reaction strength with some of the Du samples. Studies with D category cells showed that the DVI category was recognized only by hmAb 214. The reactivity pattern of this antibody is that of an anti-epD4, although the reaction strength varied greatly with different DIVa cell samples. Results obtained with hmAb 257 and 115 using papain-treated D category cells suggest that booth react as anti-epD6/7.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1994

No beneficial effect of low-dose fetal intravenous gammaglobulin administration in combination with intravascular transfusions in severe Rh D haemolytic disease.

Recent observations have shown that treatment with high-dose intravenous gammaglobulin (IVIgG) given to the mother may improve fetal outcome in cases of severe Rh D alloimmunization. Unfortunately, the costs of this new method of treatment are too high for routine use. Therefore, we decided to apply this treatment to the fetus and to investigate whether the effect of IVIgG might be attributable to blockade of the fetal mononuclear phagocyte system. We have performed a randomized study in which 20 fetuses with severe Rh D-haemolytic disease (HDN) were treated with intrauterine intravascular red cell transfusions (IUT). In 10 of these 20 cases transfusions were followed by administration to the fetus of low-dose IVIgG (85.7 +/- 11.6 mg/kg by ultrasound-estimated fetal weight because of fetal vascular volume considerations). We compared the number of IUTs, postnatal exchange transfusions, haematocrit (Ht) and haemoglobulin (Hb) values before and after transfusion (s) needed by the newborns of the two groups. No significant differences in the transfusion requirements of the fetuses and in the clinical outcome could be demonstrated. However, the 95% confidence interval for the difference in the improvement of cord blood Ht was too wide for any conclusions. The 95% confidence interval for the difference in the improvement of Hb levels suggests that any clinically relevant advantage of IVIgG on Hb is unlikely.

Blood Transfusion↗
PubMed1994

Transplacental IgG subclass concentrations in pregnancies at risk of haemolytic disease of the newborn.

The relationship of haemolytic disease of the newborn (HDN) to the transplacental passage of the four IgG subclasses was assessed at various gestational ages by comparing the maternal and fetal IgG subclass concentrations in 34 pregnancies at risk of HDN with those in 30 pregnancies not at risk. Higher maternal and fetal IgG1 levels were attained in pregnancies at risk of HDN than in pregnancies not at risk. In contrast, a slight decrease in maternal IgG2 and IgG4 levels occurred in pregnancies at risk of HDN, as compared with a slight rise in maternal IgG2 and IgG4 levels in pregnancies not at risk of HDN. Changes in fetal IgG2 and 4 concentrations in either type of pregnancy were very similar, showing only slight increases between the 19th and 34th week of gestation. A slight decrease in maternal IgG3 occurred in both types of pregnancy. In contrast, higher and fairly steady levels of fetal IgG3 were observed in fetuses not at risk of HDN throughout gestation, when compared with those in 'at risk' pregnancies. However, the statistical reliability of these results is not clear since only small numbers of samples were tested and because wide variations in IgG concentrations were observed. The IgG subclass concentrations in 50 paired maternal and cord blood samples were also measured and revealed that IgG1 levels were substantially higher in cord rather than maternal blood; cord and maternal IgG2, 3 and 4 levels, on the other hand, were fairly similar.

Erythroblastosis, Fetal↗